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Maternal hyperandrogenism is associated with a higher risk of type 2 diabetes mellitus and overweight in adolescent and adult female offspring: a long-term population-based follow-up study

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Abstract

Purpose

Adverse intrauterine environment may predispose offspring to cardio-metabolic dysfunction in later life. In this study, we aimed to investigate the effects of maternal hyperandrogenism (MH) on cardio-metabolic risk factors in female offspring in later life.

Methods

This prospective population-based study included 211 female offspring with MH and 757 female offspring without MH (controls). Both groups were followed from baseline to the date of incidence of events, censoring, or end of the study period, whichever came first. Age scaled unadjusted and adjusted cox regression models were applied to assess the hazard ratios (HR) and 95% confidence intervals (CIs) for the association of MH with pre-diabetes (pre-DM), type 2 diabetes mellitus (T2DM), overweight and obesity in offspring of both groups. Statistical analysis was performed using the software package STATA; significance level was set at P < 0.05.

Results

This study revealed a higher risk of T2DM (unadjusted HR 2.67, 95% CI 1.33–5.36) and overweight (unadjusted HR 1.41, 95% CI 1.06–1.88) in female offspring with MH, compared to controls. Results remained unchanged after adjustment for potential confounders including body mass index, education, physical activity, mother’s age at delivery, birth weight, and childhood obesity. However, no significant difference was observed in the risk of pre-DM and obesity in females with MH, compared to controls in both unadjusted and adjusted models.

Conclusion

This pioneer study with a long-term follow-up demonstrated that MH increases the risk of developing T2DM and being overweight in female offspring in later life. Further long-term population-based studies are needed to confirm these findings.

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Funding

This work was supported by the project (No. 19894) of the Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

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Authors and Affiliations

  1. Reproductive Endocrinology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, 23 Parvaneh, Yaman Street, Velenjak, Tehran, 1985717413, Iran

    M. Noroozzadeh, M. Rahmati & F. Ramezani Tehrani

  2. Faculty of Nursing and Health Sciences, Nord University, Bodo, Norway

    S. Behboudi-Gandevani

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  1. M. Noroozzadeh
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Contributions

MN contributed substantially to conception and design, analysis and interpretation of data, drafted the article and revised and approved the final version to be published. MR contributed substantially to statistical analysis of data, drafted the article and revised and approved the final version to be published. SBG contributed substantially to interpretation of data, drafted the article and revised and approved the final version to be published. FRT contributed substantially to conception and design, analysis and interpretation of data, drafted the article and revised and approved the final version to be published.

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Correspondence to F. Ramezani Tehrani.

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The authors declare that there are no conflicts of interest.

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The ethics review board of the Research Institute for Endocrine Sciences approved the study proposal (approval number: IR.SBMU.ENDOCRINE.REC.1399.015).

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Written informed consent was signed by all participants, after a full explanation of the purpose of the study to them. Written consent was obtained from their parents, if they were under 18 years old.

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Noroozzadeh, M., Rahmati, M., Behboudi-Gandevani, S. et al. Maternal hyperandrogenism is associated with a higher risk of type 2 diabetes mellitus and overweight in adolescent and adult female offspring: a long-term population-based follow-up study. J Endocrinol Invest 45, 963–972 (2022). https://doi.org/10.1007/s40618-021-01721-2

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